title: Modulation of mammary gland development in pre-pubertal mice as affected by soya and milk protein supplements.
abstract: The objective of the present study was to determine the effects of soya and whey milk protein, α-lactalbumin (α-LA), on mammary gland morphology and the structural support of the gland, in pre-pubertal mice after 7 d of treatment. In Expt 1, weaned (day 21) CD1 mice were given one of the four treatments, three included dietary supplements: (1) control diet, casein, (2) soya, (3) α-LA and (4) subcutaneous injection of 2·5 μg oestradiol benzoate in 20 μl maize oil and fed the control diet. All diets were isoenergetic with equal protein concentrations. All groups that were not treated with oestradiol received the vehicle. Whole-mount analyses were performed to determine longitudinal ductal growth and terminal end bud development. DNA was extracted from the gland and assessed by spectrophotometry (260/280 nm). Tissue extracts for extracellular matrix (ECM) proteins, matrix metalloproteinase-2 (MMP(2)), tissue inhibitor of MMP(2) (TIMP(2)), and serum oestradiol and mammary tissue epidermal growth factors (EGF) were measured by immunoassays. Expt 2 utilised the Her2/neu transgenic strain, with the same protocols. Statistical significance was determined by one-way ANOVA. From Expt 1 and 2, soya and α-LA significantly increased ductal elongation when compared with the oestrogen and control groups. These results were corroborated by data on total DNA and the ratio of MMP(2):TIMP(2). The ratio of MMP(2):TIMP(2) was affected by α-LA. Serum oestradiol was decreased only in the oestradiol-treated groups in both experiments. Soya is known to be oestrogenic and can act on epithelia directly. The mechanism by which α-LA affects glandular development is by modulating the ECM or by promoting the synthesis/activity of EGF.
authors.affiliation: North Carolina State University, Raleigh, NC 27695, USA. alstonmi@anr.msu.edu
authors.forename: Brenda
authors.initials: B
authors.lastname: Alston-Mills
authors.forename: J J
authors.initials: JJ
authors.lastname: Lepri
authors.forename: C A
authors.initials: CA
authors.lastname: Martin
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000517:prevention & control; D002364:Caseins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D004247:DNA / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000378:metabolism; D004958:Estradiol / Q000008:administration & dosage / Q000097:blood; D004968:Estrogens, Non-Steroidal / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005260:Female; D007768:Lactalbumin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D008321:Mammary Glands, Animal / Q000166:cytology / Q000254:growth & development*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D008894:Milk Proteins / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D048789:Phytoestrogens / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D011897:Random Allocation; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics; D030262:Soybean Proteins / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism; D014886:Weaning; D000067816:Whey Proteins
chemical_list: D002364:Caseins; D004247:DNA; D004815:Epidermal Growth Factor; D004958:Estradiol; D004968:Estrogens, Non-Steroidal; D016326:Extracellular Matrix Proteins; D007768:Lactalbumin; D020778:Matrix Metalloproteinase 2; D008894:Milk Proteins; D048789:Phytoestrogens; D018719:Erb-b2 Receptor Tyrosine Kinases; D030262:Soybean Proteins; D019716:Tissue Inhibitor of Metalloproteinase-2; D000067816:Whey Proteins; C524056:Erbb2 protein, mouse; C522362:Mmp2 protein, mouse